Cytosolic phospholipase A.sub.2 (cPLA.sub.2) is an arachidonic acid-specific enzyme which is of considerable interest due to its potential roles in arachidonic acid release, eicosanoid production and signal transduction. Because of these potential roles, there was interest in developing pharmaceutically effective inhibitors of cPLA.sub.2, said inhibitors being expected to be useful as, for example, anti-inflammatory agents. In this connection, there has been provided a non-radiometric, spectrophotometric assay for cPLA.sub.2 which utilizes synthetic thio-phospholipids as a substrate (Analytical Biochemistry, 217, 25-32, 1994).
As one of candidates, there is an ether-type thio-phospholipid with a wide range of physiological activities, e.g., platelet-activating factor (PAF) (1-alkyl-2-acetyl-2-deoxy-sn-glycero-3-phosphocholine) which is known as a phospho lipid mediator.
Recently, analogues of PAF which can serve as a substrate of PLA.sub.2 have been provided. For example, Tetrahedron Lett., 28, 1729 (1987) disclosed thio-PAF (1-O-hexadecyl-2-thioacetyl-2-deoxy-sn-glycero-3-phosphocholine), a derivative of PAF having 2-thioacetyl in place of 2-acetyl group. Various compounds usable as substrates and the production thereof were also disclosed in Japanese Patent Appln. Laid-open Publication No. 116279/1994. However, according to methods which have been known in the art including those described in the literatures above, the intended ether-type thio-phospholipids, especially those having thio-arachidonoyl group in sn-2 position of PAF, could not be prepared in high yield and purity. Thus, the existing methods were not efficient enough to apply to mass production of desired compounds.
Therefore, it has demanded the development of novel method of producing ether-type thio-phospholipids, which method is applicable to mass production.